Repeat-induced point mutation inNeurospora crassacauses the highest known mutation rate and mutational burden of any cellular life
Repeat-induced point mutation inNeurospora crassacauses the highest known mutation rate and mutational burden of any cellular life
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DOI：
10.1186/s13059-020-02060-w
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发表时间：
2020-06-16
期刊：
影响因子：
12.3
通讯作者：
Yang, Sihai
中科院分区：
文献类型：
--
作者：
Wang, Long;Sun, Yingying;Yang, Sihai
背景神经孢子虫的重复诱导点（RIP）突变通过靶向具有C -> T突变的重复序列来降解转座元件。RIP是否以重要的方式影响核心基因组序列尚不清楚。通过亲代-子代全基因组测序，我们估计其突变率（3.38 x 10(-6) / bp /代）比任何非病毒生物体的报道高出两个数量级，其中93-98%的突变与rip相关。然而，RIP突变在编码序列中相对罕见，部分原因是RIP优先攻击在三维空间中相互作用的gc -贫乏的长重复，而编码序列重复是罕见的，gc -丰富的，短的，并且往往不相互作用。尽管如此，每一代每个基因组有超过5个编码序列突变，突变负担比以前观察到的最高水平高出一个数量级。出乎意料的是，这些编码序列突变中的大多数似乎不是RIP的直接产物，主要是非重复序列，并且主要不是C -> T突变。尽管如此，缺乏rip的菌株在重复结构域外的编码序列突变比熟练使用rip的菌株少一个数量级。结论粗神经孢子虫在所有非病毒生命中突变率和突变负担最高。虽然高发生率主要是由于RIP的作用，但突变负担似乎与RIP相关，而不是由RIP直接引起的。
Background Repeat-induced point (RIP) mutation inNeurospora crassadegrades transposable elements by targeting repeats with C -> T mutations. Whether RIP affects core genomic sequence in important ways is unknown. Results By parent-offspring whole genome sequencing, we estimate a mutation rate (3.38 x 10(-6)per bp per generation) that is two orders of magnitude higher than reported for any non-viral organism, with 93-98% of mutations being RIP-associated. RIP mutations are, however, relatively rare in coding sequence, in part because RIP preferentially attacks GC-poor long duplicates that interact in three dimensional space, while coding sequence duplicates are rare, GC-rich, short, and tend not to interact. Despite this, with over 5 coding sequence mutations per genome per generation, the mutational burden is an order of magnitude higher than the previously highest observed. Unexpectedly, the majority of these coding sequence mutations appear not to be the direct product of RIP being mostly in non-duplicate sequence and predominantly not C -> T mutations. Nonetheless, RIP-deficient strains have over an order of magnitude fewer coding sequence mutations outside of duplicated domains than RIP-proficient strains. Conclusions Neurospora crassahas the highest mutation rate and mutational burden of any non-viral life. While the high rate is largely due to the action of RIP, the mutational burden appears to be RIP-associated but not directly caused by RIP.